Incidence Of Lymphoproliferative Disorders Research Articles

Incidence of Lymphoproliferative Disorders After Renal Transplantation is Down, but the Poor Prognosis Remains. Multicenter 32-Year Cohort Study.

Post-transplant lymphoproliferative disorders represent rare but serious complications of kidney transplantation. We assessed incidence, risk factors, and outcomes in 21,546 patients receiving grafts between 1990 and 2009. Data were compared by decade of transplant (1990-1999 vs 2000-2009). Patients were followed for at least 12 years over a 32-year study period. In total, 331 patients (1.5%) developed PTLD: 189 of 9740 transplanted in the first decade, and 142 of 11,806 in the second. Incidence decreased significantly (19.40 vs12.02 cases/1000 patients; P < .001). Mean age at diagnosis was 50.2 years (standard deviation 14.7), and the median time from transplant to PTLD diagnosis was 48 months (interquartile range, 14.7-77.5), with no difference between cohorts. The origin of PTLD was mostly (86%) B-cell proliferation. No classical risk factors were reported in 31.7% of affected patients. Compared with 2000 to 2009, in 1990 to 1999 there was a higher frequency of induction therapy (P=.023) and detection of the Epstein-Barr virus in lymphoproliferative tissue (71.3% vs 52.7% P=.019). After diagnosis, 1- and 5-year patient survival was 51% and 38%. Graft survival was 48% and 33%. Survival was stable throughout the study period. Post-transplant lymphoproliferative disorders have a low and decreasing incidence, but the poor prognosis has not changed.

Risk of Progression in Monoclonal Gammopathy of Undetermined Significance (MGUS): Results from a Population-Based Screening Study

BackgroundMonoclonal gammopathy of undetermined significance (MGUS) is a precursor condition to multiple myeloma and other lymphoproliferative disorders. In individuals with MGUS, the average risk of progression to a lymphoproliferative disorder has been estimated to be 1% per year, however, most previous studies have been performed on clinically established cohorts and very few have been population-based. A high monoclonal (M)-protein concentration, non-isotype IgG, and skewed free light chain (FLC) ratio are routinely taken into account when assessing risk for progression. Other risk factors have also been identified, such as low serum albumin.MethodsThe cohort under study consisted of 299 individuals, 158 men and 141 women, with MGUS, identified through screening the participants of the population-based, longitudinal AGES-Reykjavik Study using serum protein electrophoresis and FLC assessment. The median age was 78 years (range 67-93 years). The outcome was first incidence of lymphoproliferative disorder, denoting multiple myeloma, lymphoma, amyloidosis, lymphocytic leukemia, plasmacytoma, and Waldenström’s macroglubulinemia. Information on outcomes was supplemented by cross-linkage to national registries, and median follow-up time was 8.8 years. A Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of lymphoproliferative disorders. Results were adjusted for serum albumin in categories (below 35 g/L, 35-40 g/L, or above 40 g/L), M-protein concentration (above or below 15 g/L), FLC ratio, levels of free light chains, use of statins, smoking status, renal function in categories, and M-protein isotype. The multivariate model was reduced in a step-wise manner to a final model with only significant covariates.ResultsDuring follow-up, 26 of 299 individuals with MGUS proceeded to develop a lymphoproliferative disorder, representing a cumulative risk of 8.7% and an annual risk of 1.0%. MM occurred in 17 of 218 individuals with non-IgM MGUS, representing a cumulative risk of 7.8% and an annual risk of 0.9%.In multivariate analysis, the final model contained serum albumin, M-protein concentration, and isotype A versus all other isotypes. Low serum albumin (HR = 6.3, 95% CI 1.0-40.6 for <35 g/L, and HR = 3.9, 95% CI 1.1-14.2 for 35-40 g/L), high M-protein concentration (HR = 4.1, 95% CI 1.2-14.0), and isotype A (HR = 5.8, 95% CI 1.6-21.0) were significantly associated with risk of progression.In a similar model for progression to multiple myeloma only, low serum albumin, high M-protein concentration, and isotype A were also significantly associated with risk of progression, although the impact of low serum albumin was greater (HR = 33.1, 95% CI 2.4-462.2 for <35 g/L, HR = 10.97, 95% CI 1.4-88.3 for 35-40).When assigning a risk score for progression where 1 point each was assigned for isotype IgA, serum albumin <35 g/L, and M-protein concentration >15 g/L, the HRs for individuals with 1 point was 3.9 (95% CI 1.6-9.9), and for 2 points 10.02 (95% CI 2.3-43.3). No individual had 3 points. For Kaplan-Meier estimates from risk scores, see Figure.Summary and conclusionsIn this large, population-based screening study, we found an annual risk of progression from MGUS to lymphoproliferative disease of 1%. Low serum albumin, high M-protein concentration, and M-protein isotype A were all independent risk factors for progression. Our results are in line with results from previous studies where a low serum albumin at MGUS diagnosis also has been associated with shorter survival and/or malignant transformation. Results from our study contradict previous studies that have pointed to skewed FLC ratio as an important risk factor for progression; in our study, a skewed FLC ratio was not significantly associated with risk of progression when adjusted for other covariates. The findings in our study suggest that serum albumin is important to take into account when assessing the risk of progression for individuals with MGUS. [Display omitted] DisclosuresKorde:Medscape: Honoraria. Landgren:Merck: Honoraria; Takeda: Honoraria; Amgen: Honoraria, Research Funding; Medscape Myeloma Program: Honoraria; BMS: Honoraria; Celgene: Honoraria, Research Funding.

Accurate Real-Time Diagnosis of Lymphoproliferative Disorders in Malawi Through Clinicopathologic Teleconferences: A Model for Pathology Services in Sub-Saharan Africa.

The incidence of lymphoproliferative disorders (LPDs) is increasing in sub-Saharan Africa (SSA) due to population growth, aging, and human immunodeficiency virus (HIV). Despite significant burden, resources for diagnosis and treatment of LPDs are limited, with little infrastructure to deliver modern pathology services. Diagnostic and therapeutic decisions are therefore frequently made without tissue confirmation, leading to high rates of misdiagnosis and inappropriate treatment. We have established a laboratory in Malawi to support clinical and research efforts at a national teaching hospital. Consensus real-time diagnoses are rendered by local pathologists after weekly clinicopathologic teleconferences involving clinicians and pathologists from the United States and Malawi. Additional ancillary studies are then performed in the United States prior to final diagnosis. We report our first 2 years' experience and demonstrate high concordance between real-time diagnoses in Malawi and final diagnoses in the United States (5% major discordance rate for formalin-fixed, paraffin-embedded samples). In addition, we describe characteristics of pathologically confirmed LPDs in Malawi, highlighting differences by HIV status. Our multidisciplinary approach can be a model for strong pathology services that provide direct, real-time support to clinical care and research in SSA.

Risk of cancer in inflammatory bowel disease: going up, going down, or still the same?

There has been increasing use of immunosuppressive medications as well as better surveillance techniques in inflammatory bowel disease (IBD), which is associated with an increased risk of intestinal and extraintestinal malignancies. We assessed the temporal trends of cancer incidence in IBD patients by reviewing the biomedical literature, performing meta-regression of existing studies, and examining trends in hospitalizations for cancer in IBD patients using a national hospitalization database. The overall risk of colorectal cancer in ulcerative colitis has decreased in the last 3 decades. The risk of small bowel cancer is significantly elevated among Crohn's disease patients, but there has been no change in incidence rates. The overall risk of non-Hodgkin lymphoma has increased over the last 16 years, and IBD patients on thiopurines and antitumor necrosis factor agents are at increased risk of non-Hodgkin lymphoma. The risk of melanoma in IBD patients is increased, with no significant change over time. The risk of nonmelanoma skin cancer is higher in patients using thiopurines compared with the non-IBD background population, with no significant change over time. This study points toward a decrease in the incidence of colorectal cancer in ulcerative colitis patients, but an increase in the incidence of lymphoproliferative disorders and nonmelanoma skin cancers with the use of immunosuppressive medications in IBD.

Hemophagocytic lymphohistiocytosis caused by primary Epstein-Barr virus in patient with Crohn’s disease

We present a case of a 19-year-old man with a 6-year history of Crohn's disease (CD), previously treated with 6-mercaptopurine, who was admitted to our department for Epstein-Barr virus (EBV) infection and subsequently developed a hemophagocytic lymphohistiocytosis (HLH). HLH is a rare disease which causes phagocytosis of all bone marrow derived cells. It can be a primary form as a autosomic recessive disease, or a secondary form associated with a variety of infections; EBV is the most common, the one with poorer prognosis. The incidence of lymphoproliferative disorders was increased in patients with inflammatory bowel disease (IBD) treated with thiopurines. Specific EBV-related clinical and virological management should be considered when treating a patient with IBD with immunosuppressive therapy. Moreover EBV infection in immunosuppressed patient can occur with more aggressive forms such as encephalitis and diffuse large B cell lymphoma. Our case confirms what is described in the literature; patients with IBD, particularly patients with CD receiving thiopurine therapy, who present 5 d of fever and cervical lymphadenopathy or previous evidence of lymphopenia should be screened for HLH.

The radiological spectrum of pulmonary lymphoproliferative disease

Pulmonary lymphoproliferative disorders (LPD) are characterised by abnormal proliferation of indigenous cell lines or infiltration of lung parenchyma by lymphoid cells. They encompass a wide spectrum of focal or diffuse abnormalities, which may be classified as reactive or neoplastic on the basis of cellular morphology and clonality. The spectrum of reactive disorders results primarily from antigenic stimulation of bronchial mucosa-associated lymphoid tissue (MALT) and comprises three main entities: follicular bronchiolitis, lymphoid interstitial pneumonia and (more rarely) nodular lymphoid hyperplasia. Primary parenchymal neoplasms are most commonly extranodal marginal zone lymphomas of MALT origin (MALT lymphomas), followed by diffuse large B-cell lymphomas (DLBCLs) and lymphomatoid granulomatosis (LYG). Secondary lymphomatous parenchymal neoplasms (both Hodgkin and non-Hodgkin lymphomas) are far more prevalent than primary neoplasms. Acquired immune deficiency syndrome (AIDS)-related lymphoma (ARL) and post-transplantation lymphoproliferative disorder (PTLD) may also primarily affect the lung parenchyma. Modern advances in treatments for AIDS and transplant medicine are associated with an increase in the incidence of LPD and have heightened the need to understand the range of imaging appearance of these diseases. The multidetector CT (MDCT) findings of LPD are heterogeneous, thereby reflecting the wide spectrum of clinical manifestations of these entities. Understanding the spectrum of LPD and the various imaging manifestations is crucial because the radiologist is often the first one to suggest the diagnosis and has a pivotal role in differentiating these diseases. The current concepts of LPD are discussed together with a demonstration of the breadth of MDCT patterns within this disease spectrum.

Incidence of lymphoproliferative disorders in patients with celiac disease

Prior studies describe an increased incidence of lymphoma in celiac disease. However, few studies differentiate among lymphoproliferative disorders (LPDs). Our aim was to determine incidences of LPD subtypes in celiac disease patients, describe patterns of celiac disease presentation in patients who develop LPD, and compare survival in patients with various LPD subtypes. We conducted a retrospective cohort study of adults with biopsy-proven celiac disease seen at a US referral center from 1981 to 2010, identified patients with comorbid LPD, and calculated standardized incidence ratios (SIR) for each LPD subtype. In our cohort of 1,285 patients with celiac disease, there were 40 patients with LPD [SIR = 6.48, 95% confidence interval (CI) = 4.62-8.64] including 33 with non-Hodgkin lymphoma (NHL, SIR = 6.91, 95% CI = 4.26-8.28). The incidences of NHL subtypes including enteropathy-associated T-cell (EATL, n = 12), non-EATL T-cell (SIR = 22.43, 95% CI = 7.08-46.41), diffuse large B-cell (SIR = 5.37, 95% CI = 1.93-10.52), mantle cell (SIR = 32.21, 95% CI = 6.07-78.97), and marginal zone (SIR = 37.17, 11.73-76.89) lymphoma remained significantly elevated when only those diagnosed with celiac before LPD were considered (n = 24, NHL SIR = 4.47, 95% CI = 2.86-6.44). Patients who developed LPD were older at time of celiac disease diagnosis (57.9 ± 15.5 versus 42.5 ± 17.4 years, P < 0.0001) and more likely to present with diarrhea (60.0% versus 39.8% P = 0.016), abdominal pain (17.5% versus 5.5% P = 0.0046), and/or weight loss (12.5% versus 4.0%, P = 0.028). EATL patients had a shorter average survival than non-EATL NHL patients (3.2 versus 15.0 years, P = 0.016). The incidence of LPD is increased in celiac disease patients. Those diagnosed later in life who present with symptoms of malabsorption are more likely to be diagnosed with LPD.

26. Lymphoma arising in patients with cutaneous melanoma

Background Studies have reported an association between melanoma and lymphoproliferative disorders. We sought to determine the incidence of lymphoproliferative disorders in patients with melanoma and to characterise their clinical and pathological features. Methods Patients diagnosed with both melanoma and lymphoma between 1992 and 2007 were identified from the databases of Melanoma Institute Australia (MIA) and the Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital (RPAH). The clinical histories of the patients in the MIA database and pathology reports in the RPAH archives were reviewed. Results Between 1992 and 2007, a total of 18 226 patients were diagnosed with melanoma at MIA, of whom 55 (0.3%) patients also developed lymphoma. 23 (41.8%) patients developed a lymphoma subsequent to the diagnosis of melanoma. In seven (12.7%) patients, the melanoma was diagnosed subsequent to the lymphoma. In 25 (45.5%) patients, the lymphoma was diagnosed concurrently with the melanoma during pathological evaluation of biopsied lymph nodes. NHL was the most common lymphoma (53 patients, 96.4%), and two (3.6%) patients developed Hodgkin lymphoma. Melanoma patients had a significantly higher risk of developing NHL than the general population (standardised incidence rate 3.5). Conclusions A small but significant proportion of patients with melanoma develop lymphoma, either synchronously or metachronously. Lymph node specimens from melanoma patients may harbour lymphoma and may represent the first recognised site of disease. A high index of suspicion for lymphoma and other malignancies when evaluating lymph nodes from melanoma patients will ensure prompt diagnosis and the institution of appropriate management.

The Risk of Lymphoproliferative Disorders In Patients with Diabetes Mellitus: A Meta-Analysis

AbstractAbstract 3108 Introduction:The incidence and prevalence of lymphoproliferative disorders (LPDs) has been increasing over the past few decades. The epidemiology and risk factors associated with these malignancies continue to be in need of further research. Diabetes mellitus type 2 (DM2) has emerged as a potential risk factor for the development of LPDs, including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and plasma cell myeloma (PCM). However, the association of diabetes with specific histological subtypes of LPD is unclear. The present study evaluates the association of DM2 to common subtypes of LPD using a meta-analytical approach. Methods:MEDLINE and the Cochrane Database were searched from January 1, 1950 to December 31, 2009 for observational retrospective case-control and prospective cohort studies reporting outcomes with 95% confidence intervals (CI) on the association between DM2 and incidence of LPDs. The search keyword was “diabetes AND (chronic lymphocytic leukemia OR lymphoma OR myeloma)”. Data were gathered independently by two investigators. Disagreements were addressed by consensus. Relative risk (RR) and 95% CI were calculated using a random-effects model (REM). Heterogeneity among studies was assessed using the I2 and the Cochrane Q statistics, the quality of the studies was assessed with the Newcastle-Ottawa scale (NOS), and the dissemination bias was assessed by direct examination of a funnel plot and by the trim-and-fill analysis. Results:From a total of 1,009 returns, 12 case-control (average NOS 5.8) and 8 cohort studies (average NOS 7.6) were included in our final analysis. Sixteen studies were included for the association of NHL; four for follicular lymphoma (FL), four for diffuse large B-cell lymphoma (DLBCL), four for small lymphocytic lymphoma (SLL)/CLL, and three for peripheral T-cell lymphoma (PTCL). Seven studies were included for PCM. The overall RR for NHL in DM2 patients was 1.2 (95% CI 1.1 to 1.4; p=0.002). There was moderate heterogeneity among studies (I2=42%; Q=29.4, p=0.03). There was also minimal dissemination bias; the trim-and-fill analysis found one imputed study, which would not have affected our results. The RR for patients with FL was 0.8 (95% CI 0.6 to 1.1; p=0.15), 1.1 (0.8 to 1.4; p=0.19) for DLBCL, 1.2 (95% CI 0.9 to 1.5; p=0.33) for CLL/SLL, and 2.4 (95% CI 1.3 to 4.6; p=0.007) for PTCL. The RR for PCM in DM2 patients was 1.1 (95% CI 0.8 to 1.4; p=0.67). There was a high degree of heterogeneity among studies (I2=59%; Q=26.9, p=0.005) but there was no evidence of dissemination bias. Conclusion:The findings of this study corroborate the 20% increased risk of NHL associated with DM2. Among NHL subtypes, FL, DLBCL, nor CLL/SLL were associated with increased risk from DM2. Similarly, there was not an association between DM2 and PCM. Although a small subset, we found a 40% increased risk of PTCL in DM2 patients. Large population-based studies focusing specifically on common chronic conditions, such as DM2, and their relationship with specific LPD subtypes are needed to confirm the results of this study. Disclosures:No relevant conflicts of interest to declare.

Infliximab and Azathioprine for Crohn's Disease: A Super-Sonic Combination?

Infliximab and Azathioprine for Crohn's Disease: A Super-Sonic Combination?

Clinical Significance of EBV-Associated LPD After Cord Blood Transplantation.

Abstract 1161Poster Board I-183 IntroductionThe number of cord blood transplantation (CBT) is rapidly increasing. In this setting, development of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) appears to be at high risk. To clarify this issue, we retrospectively analyzed EBV serology and clinical course of 57 patients who received CBT during the past 12 years. Patients and methodsWe underwent 79 CBT until 2008. Fifty-seven patients were available for assessing EBV serology. The mean age of patients was 63 months (range, 6m-28y5m). The underlying disease was hematologic malignancy (n=27), hematologic non-malignancy (n=10), autoimmune disease (n=2), solid tumor (n=7), and EBV-associated T/NK-LPD (n=11). ResultsForty-six (80.7%) of the 57 recipients were EBV seropositive before CBT (sero+/). Nineteen (41.3%) of 46 EBV seropositive recipients before CBT became EBV seronegative after CBT (sero+/sero-). Five patients (8.8%) developed EBV-associated post-transplantation LPD. Three of the 5 LPD patients arose from 27 patients of sero+/sero+ group, and the time of onset of LPD was 2-6 months after CBT. Two of them died of LPD. The remaining 2 patients arose from 19 patients of sero+/sero- group, and the time of onset of LPD was 6-9 months. These 2 patients were successfully treated. None of the 11 patients (6 in sero-/sero- group and 5 in sero-/sero+ group) developed LPD. DiscussionAmong EBV seropositive patients, about 60% of them remained seropositive (endogenous infection group), and 40% of them became seronegative after CBT. The latter group is likely to experience exogenous infection (secondary primary infection). In both instances, incidence of LPD seems to be quite high. Therefore regular monitoring of EBV serology and EBV-DNA load after CBT should be essentially required for all CBT patients. DisclosuresNo relevant conflicts of interest to declare.

Trastornos linfoproliferativos en una unidad de enfermedad inflamatoria intestinal

Introduction The relationship between inflammatory bowel disease (IBD) and lymphoproliferative disorders (LD) has been previously reported. Aims To establish the local incidence of LD in an IBD unit, and to describe the clinical characteristics of observed cases. Material and methods All the clinical records of patients with ulcerative colitis (UC) or Crohn's disease (CD) followed-up in a tertiary center were reviewed. In all cases, IBD had been diagnosed according to standard criteria. Results Of 911 patients with IBD, we identified seven with lymphoma. Five of the patients were men, four had been diagnosed with UC and three with Crohn's disease. The mean time from IBD to lymphoma diagnosis was 4.82 years (r: 0–20). The mean age at lymphoma diagnosis was 53 years (r: 33–76). Four were colorectal lymphomas. There was only one case of Hodgkin's disease. Five patients had been treated with thiopurines, and four of these had also been treated with biological agents. Three cases were associated with Epstein-Barr (EBV) virus infection. The estimated incidence of LD in these IBD patients was 81.74/100,000/year. After a mean follow-up of 32.3 months (r: 5–57) following the last treatment for LD, all patients except one are in remission. Discussion The incidence rate of LD was much higher than the expected rate for the general population (81.74 vs. 22). Chronic inflammation, immune-modifying drugs and Epstein Barr virus infection may be implicated in the pathogenesis of this disease.

Multifocal Extranodal Non-Hodgkin Lymphoma Involving Both the Lungs and Brain in a Child With Primary Immunodeficiency

Immunodeficiency is associated with increased susceptibility to infections and B-cell lymphoproliferative disorders, which range from polyclonal proliferations to monoclonal lymphomas. In primary immunodeficiencies, the true incidence of lymphoproliferative disorders has been estimated between 1.4% and 24%. Recurrent or chronic infections resulting in continuous antigen exposure result in abnormal B-cell proliferation and ultimately lymphoma. Immunosuppression leads to increase in likelihood of Epstein-Barr virus-associated malignancies. We report a case of the child with multifocal extranodal non-Hodgkin lymphoma involving both the lungs and brain in a case of primary immunodeficiency.

The changing incidence of lymphoproliferative disorders in Yorkshire.

Secular trends in the incidence of lymphoproliferative disorders on North and West Yorkshire and Humberside from 1985 to 94 were studied and changes in incidence by tumour subtype were analysed. Population-based data on the incidence of lymphoproliferative disorders were obtained from a specialist registry with a high level of ascertainment. Cases of chronic lymphocytic leukaemia and plasma cell myeloma were excluded and the remaining cases classified as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). NHL were subdivided by site of origin and immunophenotype. Nodal B-cell lymphomas were further classified as diffuse large B-cell lymphoma, follicle centre lymphoma, mantle cell lymphoma and miscellaneous. During the study period there was a significant increase in total lymphoproliferative disorders with an average change of 2.5% per annum equivalent to 0.84/10,0000. Most of this increase was due to an increasing incidence of extranodal B-cell lymphomas and peripheral T-cell lymphomas. A numerically small but significant increase in diffuse large B-cell lymphomas was seen. There was no significant increase in other subtypes. The increased incidence of lymphomas in the area studied is mainly due to changes in two specific subgroups. There are several reasons why changes in extranodal B-cell lymphoma and peripheral T-cell lymphoma may have been particularly affected by changing diagnostic practices. Epidemiological studies of particular subtypes of lymphoproliferative disorder facilitate the identification of environmental factors involved in the pathogenesis of these tumours.

Peripheral blood CD3 and CD4 T-lymphocyte reduction correlates with severity of liver cirrhosis.

Immunological disturbances with impairment of immune function and a higher incidence of lymphoproliferative disorders and other malignancies have been described in liver cirrhosis patients. To investigate the pathogenetic mechanism(s) involved in such associated we looked for a possible imbalance in peripheral blood T-lymphocyte subpopulations in patients with liver cirrhosis of differing severity. Immunophenotyping and counts of peripheral blood T-lymphocyte subpopulations were carried out using monoclonal antibodies conjugated with different fluorochromes in 31 consecutive cirrhotic patients and 23 matched healthy volunteers. Univariate and multivariate analyses of lymphocyte phenotype counts were performed and odds ratios were computed. Statistically significant associations, according to both univariate and multivariate analyses, were found between case/control status and mean CD3 and CD4 T-lymphocyte counts (P < 0.0001). A strong correlation was found between the Pugh's index and CD3 and CD4 lymphocyte counts, with a clear reduction of these phenotypes with increasing liver cirrhosis. Median CD3 and CD4 values were 2,283 and 1,329/microliters respectively among controls and 896, 801, and 492/microliters and 515, 514, and 307/microliters, respectively in categories A, B, and C of Pugh's classification. Very high odds ratios were found using the median values of CD3 and CD4 as a threshold. There was a statistically significant decrease for each of the T-cell phenotypes studied (CD2, CD3, CD4, CD8, CD16, CD19, CD20, CD56, CD57) between patients and controls (P < 0.0001). The progressive and severity-related decrease in mean peripheral blood CD3 and CD4 counts in liver cirrhosis suggests a progressive impairment of protective immune function and may be a factor facilitating malignancy in cirrhotic patients.

Syndromes lympho-prolifératifs après transplantation cardiaque et traitement immunosupresseur par Ciclosporine. À propos de 4 cas

Cyclosporine is associated with and increase incidence of lymphoproliferative disorders. In heart transplantation non-Hodgkin's lymphomas (NHLs) are frequent, with a short time course for onset. Three NHLs and one multiple myeloma are reported.

The role of the Peyer's patch in carcinogenesis. II. 3-Methylcholanthrene-induced lymphoid malignancies in rat Peyer's patches.

To determine whether B or T lymphoid malignancies could be induced following the exposure of lymphoid cells within different lymphoid organs to a potential chemical carcinogen, 3-methylcholanthrene (3-MC) was directly injected into surgically exposed Peyer's patches (PP), mesenteric lymph nodes (MLN), axillary lymph nodes (ALN) or spleens (SP) of Copenhagen rats. A high incidence of lymphoproliferative disorders was observed within rats which received 3-MC injections into the PP, but not in MLN, ALN or SP injected groups of rats. In addition to the PP environment, the dose of 3-MC and exposure to pristane were important factors in the induction of T versus B cell disorders. Whereas the B cell diseases were observed in pristane-treated rats which also received PP injections of low doses (5 or 50 micrograms) of 3-MC, in animals receiving a higher dose (500 micrograms) a much higher incidence of T cell disorders was detected. The observed lymphoproliferative diseases were categorized as B lymphocytic leukemias, B lymphomas or thymic lymphomas on the basis of histological examination of the tissues, white blood cell numbers and differentials, and the morphological and phenotypic characteristics of cell isolates. Abnormal DNA staining characteristics, increased soft agar cloning frequencies and metastasis of the leukemia or tumor cells indicated that malignant cells were associated with the proliferative diseases. Collectively the data indicate that primary lymphoid malignancies of either B or T cell origins may be preferentially and reproducibly induced by localizing low or high doses respectively, of 3-MC within the PP of rats exposed to pristane. These results suggest that PP may have a possible role in the carcinogenesis of lymphocytes following the exposure to chemical carcinogens via the gastrointestinal tract.